Refining method of vegetable oils to be used as solvents for injection medicines



35- of hydrogen-ion increases closely to Patented July 19, 1932 UNITED STATES PATENT OFFICE HEISAKU EATAKEYAMLA AND HOTORI WATANABE, O F KOBE, JAPAN BEE'INING METHOD OF ,VEGETABLE OILS TO BE USED AS SOLVENTS FOR INJECTION MEDICINES No Drawing. Application filed September 7, 1929, Serial No. 391,112, and in Japan September 12, 1928.

This inventionrelates to a refining method of vegetable oils'to be used for medical purposes. It comprises removing glycerine and free fatty acids, the productsof oil by decomposition, contained in the oil to be refined, and transforming free fatty acid which possibly remain in trace in the treated oil into an ester with aromatic alcohol. The object of this invention is to obtain a neutral 1 solvent for oil-soluble substances to be used for hypodermicor muscular injection, which is never followed by irritation or pain. 7

Olive oil, for example, which has been used hitherto as a solvent of oil-soluble injecting medicine, such as camphor, has its acidity from 2 to 8 and its exponent'of hydrogen-ion is from 2 to 4. It apparently contains glycerine and free fatty acid which have been produced by decomposition of oil. The ex-' ponent of hydrogen-ion of human blood being 7, the large difference of the number between olive oil and human blood as well as the presence of free fatty acid in the oil gives intolerable pain and the injected part often suppurates, if the injected medicine is dissolved in olive oil.

According to this invention, glycerine and free fatty acids contained in vegetable oil are at first removed as completely-- as possible, and a trace of free fatty acid that cannot be removed anyhow, is neutralized by transforming same into an ester with aromatic alcohol. In this way, the acidi't of the treated oil becomes perfectly nil and its e 011%113 n account'of these facts, if the oil refined in this way is used as a solvent of an injection medicine, the unfavorable effects above mentioned can be successfully avoided.

In this invention aromatic alcohols only are used to transform free fatty acid into an ester thereof. This is because:

1. Aromatic alcohols are esterified with free fatty acids easier than fatty, alcohols.

For example, olein acid and benzyl alcohol are easily esterified when they are slightly heated, while theacid and fatty alcohol are scarcely esterified without using a catalyzer or a dehydrating agent as sulphuric acid or high pressure.

2. The ester made from an aromatic alco- 1101 and a high grade fatty acid has local narcotic effect'to human body, and when it ais absorbed into human body it is .easily oxidized and the excess of aromatic alcohol, if

any, changes into harmless hippuric acid and is excreted. Contrary to this, the fatty acids with low molecular weight, such as ethyl or methyl alcohol, gives a great pain i fication those which have OH group in sidechain of benzene ring, for example, benzyl alcohol .Oomon phenyl ethyl alcohol Oom- 011,011,

cinnamic alcohol oxybenzyl alcohol omon which has OH groups in benzene ring as well as .in side chain, and other oxyaromatic a1- cohols. These alcohols can be used in this invention, but mono and poly phenols with one or more OH groups in benzene ring should not be used, because these phenols have irrita-' tive and destructive effects to physical tissue.

This invention is further described referring to an example.

The vegetable oil to be treated should be decolored at first if itis colored one. Such decoloration can be easily attained by heat- 1 v ing the oil to'which a suitable quantity of acidic white clay and animal charcoal have been added.- Two liters of such decolored oil is taken in a flask and is heated on water bath, to which is added 300 c. c. of distilled water at atemperature of about 100 C., and

the mixture is shaken so as to make a homo-' geneous milky liquid. After it is maintained about half an hour at a temperature of from 50 to 60 C. it is poured into a separating funnel, Where the mixture sep- 4 -aratesin 3 to 4 hours into two layers oil and milky mixture of the refined oil with diswater, whereupon the water layer is re- 'moved. This washing operation shouldbe repeated several times till the removed Water becomes non-acidic. In order to remove the water which closely mixes with the oil, red heated table salt of about 50 grams or other harmless dehydrating agent which is not soluble in oil is thrown in the oil, and the latter is filtered when it becomes transparent.

In spite of such a refining treatment, the concentration number of hydrogen-ion in the tilled water is 6.3 at the largest, and this number can never be increased how many times the washing operation is repeated.

This means that a trace of free fatty acid still remains in the oil. Then 3% in volume of benzyl alcohol is addedto the oil and is heated on water bath at a temperature of about 60 C. to C. in order to esterify the free fatty acid. In order to remove the water produced due to esterification carbondioxide which has been dried by passing through sulphuric acid is bubbled in the oil. When the water is removed, the oil is heated under reduced pressure in order to remove excess benzyl alcohol which may remain in the o1 non-acidic, and the injection in which the oil is used as its solvent gives no pain at all, and there is no possibility of harming the injected part of the human body.

Claims:

1. A refining method of vegetable oils to be used as solvents for medical injection, which comprises removing the greater-portion of glycerine and free fatty acid contained in the oil, and transformlng free fatty .acid

which remain in trace in the oil into an ester by combination with an aromatic alcohol.

2. A refining method of vegetable oils to be used as solventsfor medical injection, which comprises repeatedly washing the oil with water until the washed-Water is non-acidic, and adding thereto benzyl alcohol and heating same so as to make free fatty acid in the oil esterified.

HEISAKU HATAKEYAMA. HOTORI WATANABE.

The refined oil thus obtained is perfectly 

